Study to Investigate the Nicotine Pharmacokinetic Profiles and Pharmacodynamic Effects of P4M3 Variants

Philip Morris

Status: Completed

Conditions: Nicotine Absorption; Vaping

Treatments: Other: P4M3-1.7%; Other: P4M3-1.7%LA; Other: E-cigarette; Other: P4M3-4%LA; Other: P4M3-3%LA

Study type: Interventional

Funder types: Industry

Identifiers

NCT03379740

P4M3-PK-02-US

Details and patient eligibility

About

This is a single-center, open-label, concentration-ranging study to evaluate the nicotine PK profile and PD effects in healthy adult experienced users of closed tank/cartridge e-cigarettes using four different variants of P4M3 (nicotine concentration of 1.7%, 1.7% with 1.1% lactic acid [LA], 3% with 1.1% LA, and 4% with 2% LA) or their own e-cigarettes.

Full description

The goal of the study is to evaluate the nicotine concentration profiles and derived PK parameters, subjective effects, behavioral parameters, including puffing topography parameters of P4M3 with four different variants of P4M3, in experienced e-cigarette users after a single-use experience with fixed puffing regime and after ad libitum use of P4M3.

Four variants of P4M3 will be evaluated together with subjects' own e-cigarettes to evaluate the relationship between the e-liquid composition (nicotine concentrations and presence of lactic acid) and the amount of nicotine absorbed, the speed of absorption, and the puffing topography.

Enrollment: 15 patients

Sex: All

Ages: 21 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Subject has signed the informed consent form (ICF) and is able to understand the information provided in the ICF.
• Subject is 21 to 65 years of age, inclusive, at the Screening Visit.
• Subject is a former daily cigarette smoker who smoked at least 100 cigarettes or more in his/her life and ceased smoking at least 3 months prior to the Screening Visit.
• Subject has been using a commercially available, nicotine-containing closed tank/cartridge e-cigarette daily for at least 3 months prior to the Screening Visit.
• Subject has a urine cotinine test ≥200 ng/mL at the Screening Visit and Admission.

Exclusion criteria

• Subject has a clinically relevant disease which requires medication which as per the judgment of the Investigator would jeopardize the safety of the subject.
• Subject has abnormal renal function test result or subject with a creatinine clearance <60 mL/minute at the Screening Visit, confirmed on repeat testing.
• Subject has elevated liver function test results at the Screening Visit.
• Subject has bilirubin >1.5X ULN at the Screening Visit.
• Subject has FEV1/FVC <0.7 and FEV1 <80% predicted value at post-bronchodilator spirometry at the Screening Visit.
• Subject has asthma condition at the Screening Visit.
• Subject has received medication within 14 days or within 5 half-lives of the drug (whichever is longer) prior to Admission, which has an impact on cytochrome P450 (CYP) 2A6 activity.
• Subject has a carbon monoxide (CO) breath test ≥ 10 ppm at the Screening Visit or Admission.
• Subject has a body mass index (BMI) <18.5 kg/m2 or BMI ≥35 kg/m2 at the Screening Visit.
• Subject has a positive serology test for human immunodeficiency virus (HIV) 1/2, hepatitis B, or hepatitis C at the Screening Visit.
• Subject has clinically significant ECG findings at the Screening Visit.
• Subject has participated in a clinical study within 3 months prior to the Screening Visit.
• Subject smokes cigarettes or uses other tobacco products.
• Female subject of childbearing potential who is pregnant or breastfeeding.
• Female subject of childbearing potential who does not agree to use an acceptable method of effective contraception..

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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15 participants in 2 patient groups

Product Exposure Sequence 1

Experimental group

Description:

Subjects will be randomized to follow a sequence of product exposure comprised of : Subject's own e-cigarette; P4M3-1.7%; P4M3-1.7%LA; P4M3-3%LA; and P4M3-4%LA

Treatment:

Other: P4M3-1.7%LA

Other: P4M3-1.7%

Other: E-cigarette

Other: P4M3-4%LA

Other: P4M3-3%LA

Product Exposure Sequence 2

Experimental group

Description:

Subjects will be randomized to follow a sequence of product exposure comprised of : Subject's own e-cigarette; P4M3-1.7%LA; P4M3-1.7%; P4M3-3%LA; and P4M3-4%LA

Treatment:

Other: P4M3-1.7%LA

Other: P4M3-1.7%

Other: E-cigarette

Other: P4M3-4%LA

Other: P4M3-3%LA